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Akkermansia muciniphila gavage alleviates depression-like behaviors in female A53T α-synuclein transgenic mice.

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Τίτλος: Akkermansia muciniphila gavage alleviates depression-like behaviors in female A53T α-synuclein transgenic mice.
Συγγραφείς: Li S; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China., Chu X; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China., Deng R; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China., Zheng W; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China., Suo X; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China., Sun G; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China., Liu H; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China., Geng M; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China., Tian J; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China. Electronic address: Tianjingwei618@163.com., Zhang Y; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: zhangyu5@simm.ac.cn.
Πηγή: Behavioural brain research [Behav Brain Res] 2026 Oct 18; Vol. 515, pp. 116413. Date of Electronic Publication: 2026 Aug 07.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
Ιατρικοί όροι (MeSH): alpha-Synuclein*/genetics , alpha-Synuclein*/metabolism , Depression*/metabolism , Depression*/drug therapy , Behavior, Animal*/drug effects , Behavior, Animal*/physiology , Parkinson Disease*/metabolism , Probiotics*/administration & dosage , Probiotics*/pharmacology, Serotonin/metabolism ; Hippocampus/metabolism ; Animals ; Female ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Akkermansia
Περίληψη: Parkinson's disease (PD) is characterized not only by progressive motor deficits but also by non-motor symptoms, such as depression, which often emerge during the prodromal stage and significantly impair quality of life. While Akkermansia muciniphila (AKK) has shown potential in modulating neuroinflammation, its specific role and underlying mechanisms in alleviating PD-associated non-motor symptoms remain unclear. In this study, we investigated the effects of AKK intervention in 16-month-old female A53T α-synuclein (α-syn) transgenic mice. Behavioral assessments revealed that oral administration of AKK significantly ameliorated depression-like behaviors, evidenced by reduced immobility in the forced swim test and increased sucrose preference, without affecting motor function, spatial memory, or gastrointestinal motility. Mechanistically, the intervention exhibited genotype-specific effects: AKK significantly increased plasma 5-HT levels in C57 mice. This increase was associated with an enrichment of Lactobacillus taiwanensis and metabolic pathways favoring peripheral tryptophan conversion. Conversely, in A53T mice, the treatment specifically elevated hippocampal 5-HT levels without altering plasma concentrations. This central effect correlated with distinct microbial remodeling, characterized by the enrichment of butyrate/propionate-producing Lachnospiraceae and the activation of purine degradation. Collectively, these findings provide novel mechanistic insights into the therapeutic potential of AKK for managing non-motor symptoms in PD. While limited to a female cohort, our results suggest that AKK ameliorates depression-like behaviors in PD through sex-specific remodeling of the gut microbiome and serotonergic signaling.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Akkermansia muciniphila; Depression; Gut microbiome; Parkinson's disease; α-synuclein
Substance Nomenclature: 0 (alpha-Synuclein)
333DO1RDJY (Serotonin)
SCR Organism: Akkermansia muciniphila
Entry Date(s): Date Created: 20260807 Date Completed: 20260904 Latest Revision: 20260904
Update Code: 20260905
DOI: 10.1016/j.bbr.2026.116413
PMID: 42567327
Βάση Δεδομένων: MEDLINE
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  Data: Akkermansia muciniphila gavage alleviates depression-like behaviors in female A53T α-synuclein transgenic mice.
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  Data: <searchLink fieldCode="AU" term="%22Li+S%22">Li S</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.<br /><searchLink fieldCode="AU" term="%22Chu+X%22">Chu X</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China.<br /><searchLink fieldCode="AU" term="%22Deng+R%22">Deng R</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China.<br /><searchLink fieldCode="AU" term="%22Zheng+W%22">Zheng W</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China.<br /><searchLink fieldCode="AU" term="%22Suo+X%22">Suo X</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.<br /><searchLink fieldCode="AU" term="%22Sun+G%22">Sun G</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.<br /><searchLink fieldCode="AU" term="%22Liu+H%22">Liu H</searchLink>; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.<br /><searchLink fieldCode="AU" term="%22Geng+M%22">Geng M</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.<br /><searchLink fieldCode="AU" term="%22Tian+J%22">Tian J</searchLink>; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China. Electronic address: Tianjingwei618@163.com.<br /><searchLink fieldCode="AU" term="%22Zhang+Y%22">Zhang Y</searchLink>; Shandong Laboratory of Yantai Drug Discovery (Bohai Rim Advanced Research Institute for Drug Discovery), Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: zhangyu5@simm.ac.cn.
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– Name: Abstract
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  Group: Ab
  Data: Parkinson's disease (PD) is characterized not only by progressive motor deficits but also by non-motor symptoms, such as depression, which often emerge during the prodromal stage and significantly impair quality of life. While Akkermansia muciniphila (AKK) has shown potential in modulating neuroinflammation, its specific role and underlying mechanisms in alleviating PD-associated non-motor symptoms remain unclear. In this study, we investigated the effects of AKK intervention in 16-month-old female A53T α-synuclein (α-syn) transgenic mice. Behavioral assessments revealed that oral administration of AKK significantly ameliorated depression-like behaviors, evidenced by reduced immobility in the forced swim test and increased sucrose preference, without affecting motor function, spatial memory, or gastrointestinal motility. Mechanistically, the intervention exhibited genotype-specific effects: AKK significantly increased plasma 5-HT levels in C57 mice. This increase was associated with an enrichment of Lactobacillus taiwanensis and metabolic pathways favoring peripheral tryptophan conversion. Conversely, in A53T mice, the treatment specifically elevated hippocampal 5-HT levels without altering plasma concentrations. This central effect correlated with distinct microbial remodeling, characterized by the enrichment of butyrate/propionate-producing Lachnospiraceae and the activation of purine degradation. Collectively, these findings provide novel mechanistic insights into the therapeutic potential of AKK for managing non-motor symptoms in PD. While limited to a female cohort, our results suggest that AKK ameliorates depression-like behaviors in PD through sex-specific remodeling of the gut microbiome and serotonergic signaling.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
– Name: Abstract
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  Data: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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  Data: <i>Keywords: </i>Akkermansia muciniphila; Depression; Gut microbiome; Parkinson's disease; α-synuclein
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  Label: Substance Nomenclature
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  Data: 0 (alpha-Synuclein)<br />333DO1RDJY (Serotonin)
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  Data: Akkermansia muciniphila
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  Data: <i>Date Created: </i>20260807 <i>Date Completed: </i>20260904 <i>Latest Revision: </i>20260904
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        Text: English
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        StartPage: 116413
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      – SubjectFull: Serotonin metabolism
        Type: general
      – SubjectFull: Hippocampus metabolism
        Type: general
      – SubjectFull: Animals
        Type: general
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      – SubjectFull: Mice, Inbred C57BL
        Type: general
      – SubjectFull: Akkermansia
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      – SubjectFull: alpha-Synuclein genetics
        Type: general
      – SubjectFull: alpha-Synuclein metabolism
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      – SubjectFull: Depression metabolism
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      – TitleFull: Akkermansia muciniphila gavage alleviates depression-like behaviors in female A53T α-synuclein transgenic mice.
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              Text: 2026 Oct 18
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